P1371: GRAFT-VERSUS-HOST DISEASE OFFERS NO GRAFT-VERSUS-LEUKEMIA ADVANTAGE IN PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA AFTER HAPLO-IDENTICAL STEM CELL TRANSPLANTATION WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE
Authors: A. Shimoni, C. Peczynski, M. Labopin, E. Angelucci, Y. Koc, M. Arat, J. Tischer, S. Sica, Z. Gülbas, G. Socié, D. Blaise, P. Pioltelli, H. Ozdogu, J. Vydra, F. Ciceri, A. Nagler, M. Mohty
Journal: HemaSphere (2022)

Background: The graft-versus-leukemia (GVL) effect after HLA- matched allogeneic stem-cell transplantation (SCT) in patients with acute lymphoblastic leukemia (ALL) is closely associated with graft-versus-host disease (GVHD). Patients with GVHD have a lower incidence of relapse, but at high grades a higher incidence of non-relapse mortality (NRM). The GVL effect after T-cell depleted haplo-identical SCT is mostly related to natural killer cell alloreactivity in patients with acute myeloid leukemia but not in ALL. The use of haplo-identical SCT has increased rapidly over the last decade due to the introduction of non T-cell depleted methods, in particular with post-transplant cyclophosphamide (PTCy), with expected outcomes that are similar to other donor sources. We have previously shown that in this setting GVL is not associated with GVHD in AML but there are currently no data on this association in ALL. Aims: To define the association of GVHD and GVL in ALL following non T- cell depleted haplo-identical SCT with PTCy Methods: We assessed the impact of acute and chronic GVHD on SCT outcomes in patients with ALL following non T- cell depleted haplo-identical SCT with PTCy, by using GVHD rates as time-dependent variables. Results: The study included 516 patients with ALL in first complete remission (CR1, 68%) or CR2 (32%) after non T-cell depleted haplo-identical SCT with PTCy, given during the years 2010-2019. The immune-phenotype was B-cell (75%) or T-cell (25%) and 36% were Philadelphia positive. The median age was 36 years (range, 18-75). 81% had myeloablative conditioning and 19% had reduced-intensity conditioning. The stem cell source was bone marrow (BM, 47%) or peripheral blood (PB, 54%) The 180-day cumulative incidence rates of acute GVHD grade II-IV and III-IV were 33.3% and 11.7%, respectively. The 2-year rates of chronic GVHD all grades and extensive were 35.3% and 11.8%, respectively. The 2-year rates of relapse and NRM were 27.1% and 17.3% and the rates of leukemia-free survival (LFS) and overall survival (OS), 2 years after SCT were 55.7% and 64.4%, respectively. Multivariate analysis of factors predicting relapse after SCT did not show a statistically significant effect of GVHD of any type or grade. The hazard ratios (HRs) for acute GVHD grade II, grade III-IV and limited and extensive chronic GVHD were 0.92 (0.58-1.48, P=0.74), 0.57 (0.27-1.22, P=0.15), 1.06 (0.62-1.82, P=0.83) and 0.95 (0.42-2.17, P=0.91), respectively. CR2 vs. CR1 at SCT and T-cell vs. B-cell ALL predicted for higher relapse rates with HRs of 3.18 (2.15-4.7, P<0.0001) and 1.93 (1.29-2.89, P=0.001). Relapse rates were lower in more recent years; 1-year HR 0.88 (0.81-0.95, P=0.001), respectively. The more severe GVHD grades were associated with higher NRM with HRs for acute GVHD grade III-IV and extensive chronic GVHD of 1.95 (1.09-3.48, P=0.0024) and 3.3 (1.41-7.73, P=0.006), respectively. Lower grade GVHD had no statistically significant association with NRM. Acute GVHD grade III-IV, limited and extensive chronic GVHD predicted OS with HRs of 1.91 (1.07-3.39, P=0.028), 2.29 (1.07-4.94, P=0.0034) and 3.27 (1.4-7.66, P=0.006), respectively. Summary/Conclusion: GVHD of any type or grade is not associated with reduced relapse rate after haplo-identical SCT with PTCy in ALL. Higher grades of GVHD are associated with higher NRM and lower OS. GVHD offers no GVL advantage in this SCT setting and future novel strategies for prevention of significant GVHD are warranted.